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Christmas trees are sensitive to weed competition, especially during establishment. In initial stages of the tree crop, weeds can utilize available soil moisture and trees may succumb to drought stress. In later stages, weeds can even interfere with production practices. Non-chemical weed control methods alone may not provide effective weed control. Chemical weed management strategies involve the use of preemergence and postemergence herbicides at the right timing and application rates. There are many herbicides that are used in Christmas tree production in the United States, and each has specific application guidelines and weed control spectra. Moreover, crop trees vary in tolerance by species and tree age. Growers need to be careful while applying herbicides as many of these chemicals can cause injury to Christmas trees. Repeated application of herbicides with the same mechanism of action has resulted in development of herbicide resistance among several weed species. Managing herbicide resistance has now become an important issue. More research is required on identifying and managing herbicide resistance among weed species in Christmas tree production. Future research needs to focus on herbicide and mulch combinations, herbicide rotations, and tank mixing different herbicides with different mechanisms of actions and how these affect Christmas tree varieties.

The aim of this study was to establish the ability to estimate separate airway and tissue properties from transfer respiratory impedance (Zrs,tr) data in the presence of airway obstruction. Zrs,tr, thoracic gas volume (TGV) and airway resistance (Raw,pleth) were measured in the presence of obstruction and after use of a bronchodilator (BD) in 13 normal or asymptomatic asthmatic adults and 28 children with symptomatic asthma. An analytical approach was used to solve the equations of a simplified variant of DuBois' model, including airway resistance (Raw*) and inertance (Iaw), tissue compliance (Ct) and resistance (Rt) and pulmonary gas compliance (Cg). The equations of the model could not be reliably solved in four children before BD. Mean Raw,pleth was not different from mean Raw* in adults before (mean +/- SEM) (3.4 +/- 0.5 vs 3.1 +/- 0.3 hPa.s.L-1) or after BD (1.4 +/- 0.2 vs 1.8 +/- 0.2 hPa.s.L-1), or in children after BD (2.9 +/- 0.3 vs 3.2 +/- 0.2 hPa.s.L-1, respectively). In children before BD, Raw* was significantly underestimated compared with Raw,pleth (3.8 +/- 0.4 vs 5.4 +/- 0.6 hPa.s.L-1). Overall, a significant positive correlation was found between the difference [Raw,pleth - Raw*] and Raw,pleth (r = 0.82). In adults, BD induced a decrease in Raw* and Rt, an increase in Ct, and no change in Iaw. In children after BD, there was no significant change in Raw* or Ct, whilst Rt decreased and Iaw increased. Taking Raw,pleth as the gold standard, it is concluded that coherent estimation of parameters of DuBois' model may be obtained from combined Zrs,tr and TGV measurements in normal subjects and moderately obstructed adults, but not in children with significant airway obstruction. This seems to be due to the systematic under-estimation of Raw*.

Respiratory resistance (Rrs) and elastance (Ers) are commonly measured in artificially-ventilated patients or animals by multiple linear regression of airway opening pressure (Pao) versus flow (V') and volume (V), according to the first order model: Pao = P0 + Ers.V + Rrs.V', where P0 is the static recoil pressure at end-expiration. An alternative way to obtain Rrs and Ers is to derive them from the Fourier coefficients of Pao and V' at the breathing frequency. A potential advantage of the second approach over the first is that it should be insensitive to a zero offset on V' and to the corresponding volume drift. The two methods were assessed comparatively in six tracheotomized, paralysed and artificially ventilated rabbits with and without adding to V' an offset equal to 5% of the mean unsigned flow. The 5% flow offset did not modify the results of Fourier analysis, but increased Rrs and Ers from linear regression by 15.8 +/- 4.6% and 4.55 +/- 0.64%, respectively. Without additional offset, differences between the two methods averaged 30.2 +/- 14.0% for Rrs and 9.3 +/- 6.2% for Ers. The differences almost completely disappeared (2.47 and 0.61%, respectively) when the flow signal was zero-corrected using the assumption that inspired and expired volumes were the same. After induced bronchoconstriction, however, Ers was still slightly larger by linear regression than by Fourier analysis, which may result from nonlinearities and/or frequency dependence of the parameters. We conclude that the regression method requires zero flow correction and that Fourier analysis is an attractive alternative.

Respiratory resistance (Rrs) was measured by the forced oscillation technique at 10, 20 and 30 Hz in 54 healthy subjects. The sinusoidal pressure oscillations were applied around the head, rather than at the mouth, so as to minimize transmural pressure across extrathoracic airway walls and the corresponding artefact (Peslin et al., J Appl Physiol, 1985, 59, 1790-1795). The flow (V') and volume (V) dependences of Rrs during the respiratory cycle were analysed by least square regression according to: Rrs = K1 + 2.K2.[V']#- K3.V, where K1 and K2 are Rohrer's constants, and where K3 expresses the (negative) volume dependence of Rrs. The analysis was made separately on the inspiratory and expiratory phases. A good fit was usually found between the data and the model, with a root-mean-square error averaging 15% of the mean Rrs at 10 Hz. At all frequencies K2 and K3 were substantially and significantly larger, and K1 slightly lower during expiration than during inspiration. Rrs, K1 and K3 were minimum at 20 Hz, while K2 exhibited a strong positive frequency dependence. The decrease of Rrs from 10 to 20 Hz was entirely explained by the variations of its linear component, and its increase from 20 to 30 Hz was largely due to its flow dependent component. Both the phasic variations and the frequency dependence of the coefficients suggest that the model is purely descriptive and that coefficients K2 and K3 reflect a number of phenomena, including the variations in glottic aperture during the respiratory cycle.

Total respiratory input (Zin) and transfer (Ztr) mechanical impedances were measured from 4-30 Hz in 9 patients with severe chronic obstructive pulmonary disease (COPD) and in 12 healthy subjects. Zin was obtained by applying a pressure input around the head to minimize transmural pressure across extrathoracic airway walls, and Ztr was obtained with a pressure input at the chest. In agreement with previous studies total respiratory compliance and inertance were decreased in patients, while effective input resistance was increased and exhibited a negative frequency dependence. Effective transfer resistance (Re(Ztr)) was also increased at all frequencies, and, in some patients, the Re(Ztr)-frequency curve was sigmoid in shape, which was never seen in normals. When Ztr was analysed with a six-coefficient monoalveolar model featuring tissue properties, alveolar gas compliance, and airways properties, the model fitted the data less closely in patients than in normals and, in the former, provided unrealistic coefficients. Such was also the case with a bialveolar model. A better fit with more realistic values for the coefficients was obtained in selected patients with a model where central and peripheral (Rp) airway resistance were separated by a shunt representing airway wall compliance (Cb): Cb was found to range from 0.029-0.062 l.kPa-1 and Rp represented 44-81% of total airway resistance.

At transpulmonary pressures (Ptp) of 7-12 cmH2O, pressure-volume hysteresis of isolated cat lungs has been found to be 20-50% larger than predicted from their amount of stress adaptation (J. Hildebrandt, J. Appl. Physiol. 28: 365-372, 1970). This behavior is inconsistent with linear viscoelasticity and has been interpreted in terms of plastoelasticity. We have reinvestigated this phenomenon in isolated lungs from 12 Wistar rats by measuring 1) the changes in Ptp after 0.5-ml step volume changes (initial Ptp of 5 cmH2O) and 2) their response to sinusoidal pressure forcing from 0.01 to 0.67 Hz (2 cmH2O peak to peak, mean Ptp of 6 cmH2O). Stress adaptation curves were found to fit approximately Hildebrandt's logarithmic model [delta Ptp/delta V = A - B.log(t)] from 0.2 to 100 s, where delta V is the step volume change, A and B are coefficients, and t is time. A and B averaged 1.06 +/- 0.11 and 0.173 +/- 0.019 cmH2O/ml, respectively, with minor differences between stress relaxation and stress recovery curves. The response to sinusoidal forcing was characterized by the effective resistance (Re) and elastance (EL). Re decreased from 2.48 +/- 0.41 cmH2O.ml-1.s at 0.01 Hz to 0.18 +/- 0.03 cmH2O.ml-1.s at 0.5 Hz, and EL increased from 0.99 +/- 0.10 to 1.26 +/- 0.20 cmH2O/ml on the same frequency range. These data were analyzed with the frequency-domain version of the same model, complemented by a Newtonian resistance (R) to account for airway resistance: Re = R + B/ (9.2f) and EL = A + 0.25B + B . log 2 pi f, where f is the frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Molecular Dynamics simulations in aqueous solution were performed for the matrix metalloproteinase-8 (MMP-8) free catalytic domain and for its complexes with the (R)- and (S)-[1-(4‘-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl] phosphonate. The 144−155 loop of the enzyme undergoes a drastic decrease of mobility once complexed with both enantiomers. The two enantiomers induce a different decrease of conformational entropy upon complexation. The higher affinity of the R-enantiomer can be related to the lower loss of conformational entropy accompanying its binding. The differences in the dynamical behavior of the protein induced by the two enantiomers are discussed at molecular level and the mode of binding of the simulated complexes is compared with that previously determined by X-ray crystallography.

Potent and selective inhibitors of matrix metalloproteinases (MMPs), a family of zinc proteases that can degrade all the components of the extracellular matrix, could be useful for treatment of diseases such as cancer and arthritis. The most potent MMP inhibitors are based on hydroxamate as zinc-binding group (ZBG). alpha-Arylsulfonylamino phosphonates incorporate a particularly favorable combination of phosphonate as ZBG and arylsulfonylamino backbone so that their affinity exceptionally attains the nanomolar strength frequently observed for hydroxamate analogues. The detailed mode of binding of [1-(4'-methoxybiphenyl-4-sulfonylamino)-2-methylpropyl]phosphonate has been clarified by the crystal structures of the complexes that the R- and S-enantiomers respectively form with MMP-8. The reasons for the preferential MMP-8 inhibition by the R-phosphonate are underlined and the differences in the mode of binding of analogous alpha-arylsulfonylamino hydroxamates and carboxylates are discussed.

Measurements of airway resistance (Raw) by body plethysmography during unconditioned air breathing are implicitly based on the assumption that the warming and humidification of air in the airways are instantaneous. Simulation with a simple model suggests that Raw may be frequency dependent and substantially underestimated at most breathing frequencies if the time constant of gas conditioning (theta) is between 0.01 and 0.3 s. We measured the frequency dependence of the real (Re) and imaginary parts of the relationship between the plethysmographic signal and airway flow from 0.5 to 3 Hz in six healthy subjects in several situations. During breathing of unconditioned air through a heated pneumotachograph, Re increased by 47 +/- 70% between 2 and 3 Hz; the data were consistent with a theta of 0.087 +/- 0.023 s. Additional dead spaces moderately increased theta: 0.105 +/- 0.031 and 0.120 +/- 0.027 s with 50-cm-long polyvinyl chloride and copper tubes, respectively. During breathing of saturated air conditioned at 34, 36, 38, and 40 degrees C, Re exhibited a much smaller positive frequency dependence, most of which was probably due to a flow dependence of Raw. We conclude that unless the inspired gas is conditioned, plethysmographic Raw is likely to be substantially underestimated, particularly when measured during spontaneous breathing.

The frequency dependence of respiratory mechanical properties was studied in 10 paralyzed, artificially ventilated rabbits, by superimposing a single sinusoidal signal with a frequency of 10, 20 or 30 Hz upon the ventilator waveform. The tracheal pressure and flow signals were analyzed both with the usual first order model, which provided total respiratory elastance (Ers) and resistance (Rrs), and by Fourier analysis, which provided respiratory impedance (Zrs) at the breathing frequency (0.85 Hz) and at the superimposed oscillation frequency. The real part of Zrs (Re(Zrs)) decreased by 30% from 0.85 to 10 Hz (P0.001), but did not vary significantly from 10 to 30 Hz. This finding is satisfactorily explained by tissue viscoelasticity. Following a histamine aerosol, the frequency dependence of Re(Zrs) changed very little in three out of four rabbits, but increased substantially in the fourth. In that instance, assuming that lung hysteresivity was not markedly modified by histamine, the results suggest inhomogeneous airway obstruction and/or airway wall shunting.

Changes in respiratory mechanics have occasionally been observed during high-frequency ventilation. In this study we investigated whether small pressure oscillations such as those used for respiratory impedance measurements modified total respiratory resistance (Rrs) and total respiratory elastance (Ers). The latter were measured in six paralyzed artificially ventilated rabbits with and without superimposed pressure oscillations at the airway opening. Rrs and Ers were obtained by least square fitting of low-pass filtered tracheal pressure and flow to the usual first-order model. Pressure oscillations of 2–4 hPa peak-to-peak at 10, 20, and 30 Hz applied for periods of 10 min had virtually no effect on Ers (changes ranging from -2.5 to 2.6%) and Rrs (0-8.2%). Analysis of variance did not show a significant difference on the pooled data. Pressure oscillations were also applied every other minute after a histamine aerosol. Ers and Rrs were similarly unchanged. We conclude that the small pressure oscillations used in respiratory impedance measurements do not modify lung mechanical properties and lung response to bronchomotor agents.

The aim of this investigation was to assess the optimal frequency range for analyzing respiratory transfer impedance (Ztr) in terms of tissue and airway mechanical properties using the six-element model of DuBois et al. (J. Appl. Physiol. 8:587–594, 1956). Ztr was measured in nine healthy subjects from 2 to 64 Hz by studying the relationship between airway flow and pseudorandom pressure oscillations applied around the chest. The measurements were performed with and without two mechanical loads placed at the mouth: an added inertance of 1.4 Pa.s2.l-1 and an added resistance of 1.65 hPa.s.l-1. The data were corrected for the shunt effect of upper airway walls. The changes in Ztr induced by the loads were very consistent up to 56 Hz with the T-network topology assumed in DuBois's model; the agreement deteriorated at higher frequencies, presumably due to the difficulty of obtaining a homogeneous pressure field around the chest. The fit of the model to the data also worsened sharply at above 56 Hz. In the 2- to 56-Hz frequency range, similar values of the tissue and airway coefficients were obtained with and without the loads. In that frequency range the confidence intervals of the coefficients were better than 10%. We conclude that DuBois's model is valid from 2 to 56 Hz in healthy subjects and allows accurate partitioning of airways and tissue properties. In addition, we present evidence that the upper airway shunt negligibly influences Ztr data and the derived coefficients provided airway flow is measured with a low-impedance pneumotachograph.

The upper airway wall impedance (Zuaw) may be responsible for a large artifact in the measurement of respiratory system impedance (Zrs) in children. In 17 normal children aged 3.5-13 years Zuaw and Zrs were estimated by varying transrespiratory pressure directly at the mouth (conventional method: Z1) and around the subject's head (head generator method: Z2) from 4 to 32 Hz. Zrs and Zuaw were calculated from Z1 = Zrs.Zuaw/(Zrs+Zuaw) and Z2 = Zrs (1 + Zp/Zuaw), where Zp is the impedance of the pneumotachograph. From the real and imaginary part of Z1, Z2, Zrs, and Zuaw, the corresponding resistance, inertance, compliance and resonant frequency were calculated assuming simple RIC models. No significant difference was found between the mean +/- SE of parameters derived from Zrs (respectively, 6.8 +/- 0.4 cmH2O.L-1.s, 0.034 +/- 0.001 cmH2O.L-1.s2, 10.4 +/- 0.8 m.cmH2O-1, 9.1 +/- 0.3 Hz) and Z2 (6.8 +/- 0.4 cmH2O.L-1.s, 0.038 +/- 0.002 cmH2O.L-1.s2, 10.7 +/- 0.7 ml.cmH2O-1, 8.7 +/- 0.4 Hz). All but the compliance, derived from Z1 were significantly different (P less than 0.01) from those derived from Zrs (5.3 +/- 0.3 cmH2O.L-1.s, 0.008 +/- 0.001 cmH2O.L-1.s2, 11.9 +/- 1.2 ml.cmH2O-1, and 20.3 +/- 1.6 Hz). Respiratory resistance and compliance correlated significantly with height (r = -0.56 and 0.86, respectively), in contrast to upper airway wall resistance (Ruaw) and compliance (Cuaw). Ruaw (8.6 +/- 0.8 cmH2O.L-1.s), Cuaw (1.2 +/- 0.2 m.cmH2O-1), and upper airway wall inertance (0.030 +/- 0.004 cmH2O.L-1.s2) were close to those obtained by direct measurements in adults. The mechanical properties of the upper airway wall are responsible for a significant error in the measurement of Zrs by the conventional method in normal children. Most of the artifact may be corrected for by applying pressure around the child's head.

N alpha-(N,N-dimethylcarbamoyl)-alpha-azaornitine and N alpha-(N,N-dimethylcarbamoyl)-alpha-azalysine phenyl and p-nitrophenyl esters (7-10) were synthesized and tested as inhibitors of trypsin, chymotrypsin and thrombin. The N,N-dimethylcarbamoyl group was chosen to decrease the tendency of acylcarbazates to cyclization into 1,3,4-oxadiazol-2(3H)-ones. Only the p-nitrophenyl alpha-azaornithine derivative 8 was inactivated rapidly by intramolecular acylation of the terminal amino group, rather than by cyclization to oxadiazolone, in aqueous solution at pH 8. The corresponding alpha-azalysine derivative 10 is completely unaffected under the same conditions. Rapid inactivation of thrombin and trypsin only was observed for all alpha-azapeptide esters 7-10 at 0.5 mM inhibitor concentration. No proteolytic activity was restored after 24 h following 2,000 fold dilution of the inhibitor concentration suggesting formation of very stable acylenzymes.

Fifteen 1-peptidyl-2-haloacetyl hydrazines, which can be considered halometanes of azapeptides containing Phe in P2 and alpha-aza-Ala or alpha-aza-Gly in P1, were synthesized and tested as models of cysteine-proteases inhibitors. By use of kinetic methods, they proved to irreversibly inactivate papain and cathepsin B via a reversible enzyme-inhibitor intermediate. Second-order rate constants of inactivation in the range 26-23000 M-1s-1 were observed for papain and 2000-39600 M-1s-1 for cathepsin B. KI for the reversible EI adducts ranged from 230 to 0.16 microM for papain and from 11 to 0.37 microM for cathepsin B. Structure of possible reversible EI complex is proposed and used to discuss the effects of structural variation of the inhibitors on the kinetic parameters of inactivation. Title compounds proved to be selective for cysteine-proteases, since no inhibiting activity could be detected toward trypsin, chymotrypsin and porcine pancreatic elastase at 0.1 mM concentration, after 6 h incubation. Relatively low aspecific alkylating properties were also verified in tests using glutathione as the nucleophile.

The MRL-lpr murine model of systemic lupus erythematosus (SLE) has provided many insights into the pathology of human lupus. The model is characterized by an age-dependent expansion of a Thy-1+ αβ CD3 + CD4−, CD8− T-cell subset in the nodes and spleen. In this study, a lpr T-cell specific monoclonal antibody, Ye19.1, was found to bind to a 200 kDa cell surface molecule (termed LTA) which has a phosphotyrosine phosphatase (PTPase) enzymatic function. The significance of this marker in the development of autoimmune pathology in MRL lpr mice was also demonstrated; treatment of MRL-lpr mice with the Ye19.1 Ab was shown to retard the development of the autoimmune syndrome and to restore the T cell-dependent immune response to ovalbumin.

Short-term intraindividual variability of the parameters derived from respiratory transfer impedance (Ztr) measured from 4 to 32 Hz was studied in 10 healthy subjects. The corresponding 95% confidence intervals (CIo) were compared with those computed from a single set of data (CIL) according to Lutchen and Jackson (J. Appl. Physiol. 62: 403-413, 1987). Ztr was analyzed with the six-coefficient model of DuBois et al. (J. Appl. Physiol. 8: 587-594, 1956), which includes airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility (Cg). The lowest variability was seen for Iaw (CIo = 11.1%), closely followed by Raw (14.3%) and Cti (14.8%), and the largest for Rti and Iti (24.6 and 93.6%, respectively). Using a simpler model, where Iti was excluded, significantly decreased the variability of Iaw (P less than 0.01) and Rti (P less than 0.05) but was responsible for a systematic decrease of Raw and Iaw and increase of Rti. Except for Raw with both models and Iaw with the simpler model, CIL was greater than CIo. Whatever the model, a high correlation between both sets of confidence intervals was found for Rti and Iaw, whereas no correlation was seen for Raw. This suggests that the variability of the former coefficients mainly reflects experimental noise, whereas that of the latter is largely due to biological variability.

Respiratory impedance may be studied by measuring airway flow (Vaw) when pressure is varied at the mouth (input impedance) or around the chest (transfer impedance). A third possibility, which had not been investigated so far, is to apply pressure variations simultaneously at the two places, that is to vary ambient pressure (Pam). This provides respiratory impedance to ambient pressure changes (Zapc = Vaw/Pam). In that situation airway impedance (Zaw) and tissue impedance (Zt) are mechanically in parallel, and both are in series with alveolar gas impedance (Zg): Zapc = Zaw + Zg + Zaw.Zg/Zt. We assessed the frequency dependence of Zapc from 0.05 to 2 Hz in nine normal subjects submitted to sinusoidal Pam changes of 2-4 kPa peak to peak. The real part of Zapc (Rapc) was of 6.2 kPa.1(-1).s at 0.05 Hz and decreased to 1.9 kPa.1(-1).s at 2 Hz. Similarly the effective compliance (Capc), computed from the imaginary part of Zapc, decreased from 0.045 1.kPa-1 at 0.05 Hz to 0.027 1.kPa-1 at 2 Hz. Breathing against an added resistance of 0.46 kPa.1(-1).s exaggerated the negative frequency dependence of both Rapc and Capc. When values of airway resistance and inertance derived from transfer impedance data were introduced, Zapc was used to compute effective tissue resistance (Rt) and compliance (Ct). Rt was found to decrease from 0.32 to 0.15 kPa.1(-1).s and Ct from 1.11 to 0.64 1.kPa-1 between 0.25 and 2 Hz. Ct was slightly lower with the added resistance. These results are in good agreement with the data obtained by other approaches.

Differential pressure transducers are commonly used to study respiratory mechanics at physiological frequencies as well as during external forcing at high frequencies. In the latter condition, measuring errors could occur if the input impedance of the pressure transducers is not sufficiently large with respect to that of the respiratory system. In this work we analysed the input impedance Z and the transfer function H of two common pressure transducers (Validyne MP-45 and Celesco LCVR) equipped with membranes of different sensitivities and with connecting tubes of different lengths. Z was measured by the tube method and H was measured by comparison with a flat-response pressure transducer. In agreement with the predictions based on a simple lumped-parameters model, we found that Z reached very low values, especially at the frequencies where H had a resonance peak. For instance, for the widespread Validyne MP-45 transducer (200 Pa) with connecting tubes of 16 cm length and 3.8 mm internal diameter a minimum of Z of 8300 Pa s litre-1 at 96 Hz was measured; at that frequency the amplitude of H attained a value of 3.1. Using the above transducer model we simulated the measurement of a rat input impedance up to 128 Hz using Validyne and Celesco transducers. With the Validyne MP-45 (200 Pa), equipped with the same connecting tubes as above, the computed error reached up to 50 per cent for the real part and 140 per cent for the imaginary part.

The validity of a new method for measuring thoracic gas volume (TGV) was studied in 69 children, 4-16 yrs old, including twelve normal children and 57 children with an obstructive (n = 38) or restrictive (n = 19) respiratory disease. The method consisted of applying very slow (0.05 Hz) sinusoidal variations of ambient pressure around the body (delta Pam = 40 cmH2O peak to peak) and studying the relationship between delta Pam and the resulting gas displacement at the mouth (Vaw): TGVapc = PB.delta Vaw/delta Pam.cos phi, where PB is barometric minus alveolar water vapour pressure and phi the phase angle between Pam and Vaw. Functional residual capacities derived from TGVapc (FRCapc) were compared to the values obtained by plethysmography (FRCplet) and by helium dilution (FRCdil). FRCapc did not differ significantly from FRCplet in either the entire group (1.75 +/- 0.62 l vs 1.79 +/- 0.45 l) or in the patient subgroups. However, with the new method a trend to slightly lower FRCs was seen in patients with the most obstruction (p less than 0.05). FRCdil was significantly lower than both FRCapc and FRCplet (p less than 0.001), particularly in children with obstruction. Significant correlations were found between the three methods (p less than 0.001). On the other hand, the method investigated requires that the subject breathe very regularly for a period of several minutes. This was rarely achieved, so that the reproducibility of the measurements was unacceptably low. At present, the method cannot be recommended for routine use in 4-16 yr old children.

The validity of a new method for measuring thoracic gas volume (Vtg) was studied in 18 bronchitic patients with mild to severe airway obstruction. The method entailed submitting the subject to very slow sinusoidal variations of ambient pressure (delta Pam) and studying the relationship between delta Pam and the resulting gas displacement at the mouth (delta Vaw): Vtgapc = PB.delta Vaw/delta Pam.cos phi, where PB is barometric minus alveolar water vapor pressure, and phi is the phase angle between Pam and Vaw. delta Pam of 40 cm H2O at 0.05 Hz were achieved by placing the subject in a 410-I body chamber connected to a large stroke volume reciprocating pump. Pam and Vaw were processed digitally by Fourier transform to obtain their amplitude ratio and phase angle at the frequency of interest. Vtg was also measured by body plethysmography (Vtgplet) during slow panting maneuvers (0.79 +/- 0.19 Hz) and also in order to detect any artifactual frequency dependence at a higher panting frequency (1.71 +/- 0.27 Hz); the agreement between the 2 estimates in all subjects (r = 0.975) suggested that Vtgplet could be taken as a valid reference. Functional residual capacities derived from Vtgapc and Vtgplet were not significantly different (5.113 +/- 1.198 versus 5.260 +/- 1.328 L) and were highly correlated (r = 0.915). Intermethod differences averaged 1.7 +/- 10.5% and were not significantly correlated to functional indices. We conclude that the new method provides accurate Vtg values in patients with chronic airway obstruction.

The influence of inspiratory and expiratory flow magnitude, lung volume, and lung volume history on respiratory system properties was studied by measuring transfer impedances (4-30 Hz) in seven normal subjects during various constant flow maneuvers. The measured impedances were analyzed with a six-coefficient model including airway resistance (Raw) and inertance (Iaw), tissue resistance (Rti), inertance (Iti), and compliance (Cti), and alveolar gas compressibility. Increasing respiratory flow from 0.1 to 0.4 1/s was found to increase inspiratory and expiratory Raw by 63% and 32%, respectively, and to decrease Iaw, but did not change tissue properties. Raw, Iti, and Cti were larger and Rti was lower during expiration than during inspiration. Decreasing lung volume from 70 to 30% of vital capacity increased Raw by 80%. Cti was larger at functional residual capacity than at the volume extremes. Preceding the measurement by a full expiration rather than by a full inspiration increased Iaw by 15%. The data suggest that the determinants of Raw and Iaw are not identical, that airway hysteresis is larger than lung hysteresis, and that respiratory muscle activity influences tissue properties.

A new method of studying the linearity of gas flowmeters was tested on different models of Fleisch pneumotachographs. The method applies a steady flow to the test flowmeter, which is increased in a stepwise manner by adding a constant flow-increment. This is achieved using two flow sources in parallel. The method does not require any reference flow channel and may be implemented with standard laboratory equipment. Using this method, the gain of Fleisch pneumotachographs, whatever their size, decreased by about 2-3% from low flows to about 40% of their nominal full scale (FS), and then increased almost linearly with increasing flow. The error was 8-13% at 200% FS. The following equation was devised to correct the data at high flow: Vc = Vt (1-K (Vt-S] where Vc and Vt are the corrected and measured flow respectively, K a gain correction factor and S a flow threshold below which no correction is needed. Applying this correction with suitable coefficients, the maximal error was below 3% from 0-200% FS.

Total respiratory input (Zrs,in) and transfer (Zrs,tr) impedances were obtained from 4 to 30 Hz in 10 healthy males by simultaneously measuring mouth and chest flow while applying pseudo-random pressure variations at the mouth. Compared with Zrs,in, the real part of Zrs,tr was larger up to 10 Hz but exhibited a much stronger negative frequency dependence. The imaginary part was larger at all frequencies, with a resonant frequency (fn) at 6.0 +/- 0.8 Hz compared with 8.2 +/- 2.9 Hz for Zrs,in. The two impedances were analyzed with a model featuring airway resistance and inertance, alveolar gas compressibility, and tissue resistance, inertance, and compliance. A good fit was generally obtained but, in most cases, with a different partitioning of resistance between airway and tissue for Zrs,in and Zrs,tr. The data were also used to compute separately airway and tissue (Zt) impedances. In most subjects Zt could not be properly fitted with a simple resistance-inertance-compliance unit and was consistent with a slow (fn = 7.4 +/- 2.3 Hz) overdamped compartment in parallel with a fast (fn = 37.1 +/- 5.6 Hz) underdamped one.

Total respiratory input (Zin) and transfer (Ztr) impedances were obtained from 4 to 30 Hz in 10 healthy subjects breathing air and He-O2. Zin was measured by applying pressure oscillations around the head to minimize the upper airway shunt and Ztr by applying pressure oscillations around the chest. Ztr was analyzed with a six-coefficient model featuring airways resistance (Raw) and inertance (Iaw), alveolar gas compressibility, and tissue resistance, inertance, and compliance. Breathing He-O2 significantly decreased Raw (1.35 +/- 0.32 vs. 1.74 +/- 0.49 cmH2O.l-1.s in air, P less than 0.01) and Iaw (0.59 +/- 0.33 vs. 1.90 +/- 0.44 x 10(-2) cmH2O.l-1.s2), but, as expected, it did not change the tissue coefficients significantly. Airways impedance was also separately computed by combining Zin and Ztr data. This approach demonstrated similar variations in Raw and Iaw with the lighter gas mixture. With both analyses, however, the changes in Iaw were more than what was expected from the change in density. This indicates that factors other than gas inertance are included in Iaw and reveals the short-comings of the six-coefficient model to interpret impedance data.

The real--Re(Z)--and imaginary--Im(Z)--parts of the ventilatory system impedance were measured between 6 and 30 Hz in 18 normal infants and in 19 with airway obstruction. The intercept (R0) and slope (S) of the Re(Z)-frequency function, as well as inertance (I) and compliance (C) estimated from Im(Z), were compared with ventilatory system resistance (Rrs) and compliance (Crs) (single-breath method). R0 correlated significantly with Rrs (r = 0.86), although the slope of the regression equation was significantly lower than 1 (P less than 0.01). Negative frequency dependence of Re(Z) was observed in all subjects and a significant correlation was found between S and Rrs (r = -0.80). "Inertance" was negative in 20 subjects and correlated negatively with Rrs (r = -0.61). C correlated with Crs (r = 0.64) and with 1/Rrs (r = 0.85). The ratio of C to Crs (mean +/- SD = 0.168 +/- 0.082) also correlated with 1/Rrs (r = 0.51). The main characteristics of the total impedance/frequency function could be simulated with a model featuring the upper airway wall (Zuaw) in parallel with the ventilatory system (Zrs). It is suggested that the differential change in Zuaw and Zrs with growth accounts for the marked frequency dependence of Re(Z) as well as the inaccurate estimation of both I and C in this population.

Regio and stereochemistry of the title reaction appear to be strongly influenced by the nature of both organometallic and allylic reagents. The results are discussed in view of the intervention of ion-pair intermediates.

Condensation of 1,4-diacetylpiperazine-2,5-dione with aldehydes has been applied to the synthesis of albonoursin and unsymmetrical 3,6-diarylidenepiperazine-2,5-diones. The reaction has been extended to 1,4-diacetyl-3,6-dimethylpiperazine-2,5-dione, which gives derivatives of 2-methyl-3- phenylserine. The mechanism and stereochemistry are discussed; cis 1-acetyl-3-isobutylidene- piperazine-2,5-dione has been isolated.

The isomeric alkenes 1 – 4 have been obtained by syn , γ substitution of the appropriate allylic carbamates with Li2Cu3Me5. The behaviour of carbamates is deeply affected by the nature of the copper reagent.

When the whole body is exposed to sinusoidal variations of ambient pressure (delta Pam) at very low frequencies (f), the resulting compression and expansion of alveolar gas is almost entirely achieved by gas flow through the airways (Vaw). As a consequence thoracic gas volume (TGV) may be computed from the imaginary part (Im) of the delta Pam/Vaw relationship: TGV = PB/[2 pi f X Im(delta Pam/Vaw)], where PB is barometric minus alveolar water vapor pressure. The method was tested in 35 normal subjects and compared with body plethysmography. The subjects sat in a chamber connected to a large-stroke-volume reciprocating pump that brought about pressure swings of 40 cmH2O at 0.05 Hz. delta Pam and Vaw were digitally processed by fast Fourier transform to extract the low-frequency component from the much larger respiratory flow. Total lung capacities (TLC) obtained by ambient pressure changes and by plethylsmography were highly correlated (r = 0.959, p less than 0.001) and not significantly different (6.96 +/- 1.38 l vs. 6.99 +/- 1.38). TLC obtained by ambient pressure changes were not influenced by lowering the frequency to 0.03 Hz, adding an external resistance at the mouth, or increasing abdominal gas volume. We conclude that the method is practical and in agreement with body plethysmography in normal subjects.

Alveolar gas volume (AGV) may be measured in humans (Peslin et al., J. Appl. Physiol. 62: 359-363, 1987) by applying very slow sinusoidal variations of ambient pressure (delta Pam) around the body and studying the relationship between delta Pam and the resulting gas displacement at the mouth (delta Vaw): AGVapc = (PB.delta Vaw)/(delta Pam.cos phi), where AGVapc is AGV measured by ambient pressure changes, PB is barometric minus alveolar water vapor pressure, and phi is the phase angle between Pam and Vaw. The applicability of this method to excised lungs at various transpulmonary pressures was assessed in six rabbit lungs and three dog lobes by reference to AGV measurements by He dilution (AGVdil) and by a volumetric method (AGVvol). Except in one instance, AGVapc did not change significantly when the frequency of delta Pam was varied from 0.02 to 0.2 Hz. AGVapc was highly correlated (P less than 0.001) to both AGVdil and AGVvol. It did not differ significantly from AGVdil (81.4 +/- 50.6 vs. 80.2 +/- 44.2 ml) and was only marginally higher than AGVvol (64.6 +/- 26.9 vs. 62.4 +/- 24.4 ml, P less than 0.05). We conclude that the method usually provides accurate results in excised lung preparations. Its main advantages are that it does not require manipulating the lung or changing its volume and that the measurement takes less than 1 min.

cis -3-Guanidino-L-proline and capreomycidine have been obtained by catalytic hydrogenation of viomycidine. The configuration of the 3-aminoproline isolated in the alkaline hydrolysis of guanidinoproline has been determined by means of ORD data and DAO oxidation. Assignement of trans geometry to the 3-aminoproline is based on the synthesis of both the cis and trans 3-aminoprolines.

Thoracic gas volume (TGV) and specific airway resistance (sRaw) are commonly measured using pressure type and flow type body plethysmographs. Within-subject variability of the data, defined as the coefficient of variation of eight to ten measurements during the same session, was assessed with the two kinds of instruments and compared in fifteen normal subjects. The reproducibility of data obtained several days apart was also compared. All measurements were made in a 480-l body chamber, which could be used in both the pressure and the flow mode. The signals were processed digitally using three different algorithms: 1) simple linear regression (LR); 2) linear regression with drift correction achieved by adding to, or subtracting from the plethysmographic signal a term proportional to time (LRC); 3) Fourier analysis (FFT). Within-subject variability of TGV was much larger with flow than with pressure plethysmography when the signals were processed by LR (14.5 +/- 7.5 vs 6.3 +/- 3.0%; p less than 0.001), but almost the same using LRC (6.7 +/- 3.2 vs 5.4 +/- 2.7%) and FFT (6.1 +/- 2.4 vs 5.0 +/- 2.4%). For sRaw, variabilities were larger and less influenced by methodological factors. Adequate digital processing may therefore largely remedy the inherently greater variability of TGV measurements with flow plethysmographs.

A new method for measuring total respiratory input impedance (Zrs), which ensures minimal motion of extrathoracic airway walls, was tested over frequencies of 4–30 Hz in 14 normal subjects and 10 patients with airway obstruction. It consists of applying pressure variations around the head, rather than at the mouth, so that transmural pressure across upper airway walls is equal to the small pressure drop across the pneumotachograph. Compared with reference Zrs values obtained by directly measuring airway wall motion with a head plethysmograph and correcting the data for it, the investigated method provided similar values for respiratory resistance at all frequencies (30 Hz, 3.67 +/- 2.24 cmH2O X 1(-1) X s compared with 3.55 +/- 2.00) but slightly overestimated respiratory reactance at the largest frequencies (30 Hz, 2.82 +/- 1.28 cmH2O X 1(-1) X s compared with 2.52 +/- 1.22, P less than 0.01). In contrast, when the data were not corrected for airway wall motion, resistance was largely underestimated, especially in patients (-48% at 30 Hz, P less than 0.001), and the reactance-frequency curve was shifted to the right. The investigated method is almost as accurate as the reference method, provides equally reproducible data, and is much simpler.

We investigated two methods of decreasing the error on plethysmographic determinations of thoracic gas volume (TGV) related to cheeks movements during panting maneuvers: lowering gas density in the airways with an 80% He-20% O2 mixture and computing TGV from the in-phase component of the plethysmographic signal (TGVr). The methods were tested by measuring how TGV estimates varied when panting frequency was raised from 0.8 to 2.5 Hz during the same occlusion. The measurements were performed in 6 normal subjects and 12 patients with chronic bronchitis with and without cheeks support and when the airway was connected to an external device simulating an increased cheeks compliance. A small negative frequency dependence of TGV (delta TGV/delta f = -1.2 +/- 0.8%/Hz with cheeks support), most probably unrelated to upper airway walls, was found in normal subjects. Delta TGV/delta f was positive and algebraically larger in patients than in normals, reaching 2.2 +/- 3.4%/Hz without cheeks support and 11.8 +/- 8.0%/Hz with the additional cheeks. The latter value was only 20% smaller when computed on the basis of TGVr, demonstrating the limited usefulness of the phase-based correction. In contrast, breathing He-O2 decreased delta TGV/delta f to approximately 50% of its air value (P less than 0.01) and appears as an effective way to diminish the error in obstructive patients.

When studying respiratory impedance by forced oscillations, part of the flow measured at the mouth is lost in upper airway wall motion and does not enter the trachea. The corresponding error was studied in 10 normal subjects and 8 patients with chronic obstructive pulmonary disease (COPD) by measuring respiratory impedance with the cheeks unsupported, with the cheeks supported, and when upper airway wall motion was simultaneously measured with a head plethysmograph, and corrected for. In normal subjects, wall motion had little influence on respiratory resistance but, whether the cheeks were supported or not, increased the resonant frequency (p less than 0.05) and respiratory compliance (p less than 0.001) and decreased respiratory inertance (p less than 0.001). In patients with COPD, average resistance from 4 to 30 Hz was significantly lower when the cheeks were not supported (3.32 +/- 0.57 cm/H2O X L-1 X s; m +/- SD) than when they were (4.59 +/- 0.73, p less than 0.01) and when the data were corrected (5.41 +/- 1.14, p less than 0.001). Moreover, resistance increased with increasing frequency when wall motion was corrected for and decreased when it was not. Upper airway wall motion also tended to increase resonant frequency and decrease inertance in patients. The data show that supporting the cheeks does not prevent large errors on respiratory impedance and derived parameters, especially in obstructive patients; accurate measurements require that airway wall motion be evaluated and corrected for.

Total respiratory impedance was obtained from 4 to 30 Hz in 39 healthy males and in 140 iron miners by studying the relationship between transrespiratory pressure and mouth flow when forced oscillations were applied to the respiratory system in two different ways: by varying pressure at the mouth (input impedance, Zin); by varying pressure around the chest (transfer impedance, Ztr). Zin was characterized by the slope (S) and intercept (R0) of the resistance-frequency curve, by the resonant frequency (fn), and by total respiratory inertance (I) and compliance (C) obtained from the reactance. Transfer resistance and reactance curves were respectively analysed with a two-parameter (m1, m3) and a three-parameter (m0, m2, m4) equation. Significant correlations were found between impedance indices, particularly between m1 and both R0 (r = 0.931; p less than 0.001) and m2 (r = 0.739; p less than 0.001), and also between impedance indices and maximal expiratory flows. Nonsmoking miners (n = 40), compared to control nonsmokers (n = 16), had slightly lower maximal flows at high lung volumes (p less than 0.05) and higher values of m1 (p less than 0.001), R0, S, m3 (p less than 0.01) and m2 (p less than 0.05). In contrast, miners who smoked (n = 46) mainly differed from miners who did not smoke by lower flows at middle and low lung volumes (p less than 0.01) and larger m0 (p less than 0.01), m2 and m4 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Reference values for respiratory impedances in children are scarce and limited to the situation where pressure is varied at the mouth. Total respiratory impedance was therefore measured from 4 to 30 Hz in 69 healthy children (9-13 yr) with both a pressure input at the mouth (input impedance, Zin) and a pressure input at the chest (transfer impedance, Ztr). Zin was characterized by the average resistance (R), the low-frequency limit of resistance (R0), the slope of the resistance-frequency curve (S), respiratory elastance (E) and respiratory inertance (I). Similar coefficients (R0', S', E', I'), some of which however have slightly different physiological meanings, were derived from Ztr. R, R0 and R0' were found to be significantly correlated to body height (p less than 0.001) and, independently, to age (p less than 0.05): R (kPa X l-1 X s) = 1.76-5.29 10(-3) height (cm) -4.13 10(-2) age (yr). Elastances were better correlated to height than to age: E (kPa X l-1) = 20.95-0.101 height (cm) and inertances better correlated to age than to height: I (Pa X l-1 X s2) = 4.39-0.128 age (yr). S and S' were not correlated to biometric variables. No difference was found between children living in polluted (n = 36) and nonpolluted (n = 33) areas, except for S which was significantly lower in the first group (p less than 0.01).

Two methods of measuring ventilatory mechanical impedance (Z) by forced oscillations between 6 and 20 Hz were compared in 24 infants aged 2 to 49 months: 1) the application of pressure oscillations at the airway opening (Z1); and 2) the application of pressure oscillations around the head (Z2). The latter has been recently proposed to minimize the influence of compliant upper airway walls (Peslin et al., J Appl Physiol. 1985, 59:1790-1795). Ventilatory resistance and compliance (Rsb, Csb) were also obtained with the single breath method. The real part of Z1 (R1) was markedly lower than that of the corresponding Z2 (R2), at any frequency. R1 exhibited a systematic negative frequency dependence, in contrast with R2. At any frequency, the slope of the regression equation on Rsb was closer to unity for R2 than for R1. The imaginary part of Z1 (X1) was negative over the whole frequency interval, and negative values of inertance were derived from X1. X2 was negative at low and positive at high frequencies. Resonant frequency (mean +/- SD = 10.5 +/- 3.5 Hz) was always reached with Z2 and correlated negatively with body weight (r = -0.61). Inertance estimated from X2 was positive and correlated negatively with body height (r = -0.66). The compliance derived from Z1 (C1 = 3.35 +/- 2.32 10(-3) L.cm H2O-1) was not significantly different from that derived from Z2 (C2 = 2.99 +/- 2.02 10(-3) L.cm H2O-1). The marked difference observed between Z1 and Z2 is related to the importance of the upper airway shunt and may be explained by inaccuracies of both methods.(ABSTRACT TRUNCATED AT 250 WORDS)